Famotidine

Description

The active ingredient in famotidine for oral suspension, USP, is a histamine-2 (H2) receptor antagonist. Famotidine, USP is chemically designated as N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide, with an empirical formula of C8H15N7O2S3 and a molecular weight of 337.43.

Each 5 mL dose of famotidine for oral suspension, USP, when prepared as directed, contains 40 mg of famotidine, USP, along with inactive ingredients including carboxymethyl cellulose sodium, flavors (banana, cherry, and peppermint), fumaric acid, microcrystalline cellulose, sucrose, and xanthan gum. Preservatives included are sodium benzoate (0.42%), sodium methyl paraben (0.08%), and sodium propyl paraben (0.02%).

Famotidine, USP appears as a white to pale yellow-white crystalline compound. It is freely soluble in dimethylformamide and glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol, chloroform, ether, and ethyl acetate.

Uses and Indications

Famotidine for oral suspension is indicated for the treatment of active duodenal ulcers (DU) and active gastric ulcers (GU). It is also indicated for symptomatic nonerosive gastroesophageal reflux disease (GERD) and erosive esophagitis due to GERD, which must be diagnosed by biopsy. Additionally, this medication is used in the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Famotidine is effective in reducing the risk of DU recurrence.

In pediatric patients aged 1 year and older, famotidine is indicated for the treatment of peptic ulcers and GERD, with or without esophagitis and ulcerations. For pediatric patients from birth to less than 1 year of age, famotidine is indicated specifically for the treatment of GERD.

There are no teratogenic or nonteratogenic effects associated with famotidine as per the available data.

Dosage and Administration

The recommended adult dosage varies by indication. For active duodenal ulcers (DU), the dosage is 40 mg once daily or 20 mg twice daily. In cases of active gastric ulcers (GU), the dosage is 40 mg once daily. For symptomatic nonerosive gastroesophageal reflux disease (GERD), the recommended dosage is 20 mg twice daily. In the treatment of erosive esophagitis due to GERD, the dosage may be 20 mg twice daily or 40 mg twice daily. For pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to patient needs, not exceeding a maximum of 160 mg every 6 hours. To reduce the risk of DU recurrence, a dosage of 20 mg once daily is recommended.

For pediatric patients, the dosage for peptic ulcer disease in children aged 1 year to less than 17 years starts at 0.5 mg/kg once daily or 0.25 mg/kg twice daily, with the possibility of increasing to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily, not exceeding a maximum of 40 mg per day. For GERD in infants from birth to less than 3 months, the starting dosage is 0.5 mg/kg once daily, which may be increased to 1 mg/kg once daily. In children aged 3 months to less than 1 year, the starting dosage is 0.5 mg/kg twice daily, with a potential increase to 1 mg/kg twice daily, also not exceeding 40 mg per day. For GERD with or without esophagitis and ulcerations in children aged 1 year to less than 17 years, the recommended dosage is 0.5 mg/kg twice daily, with a maximum of 40 mg twice daily.

Administration should occur once daily before bedtime or twice daily in the morning and before bedtime, with or without food.

Contraindications

Use is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to famotidine or other H2 receptor antagonists. This contraindication is due to the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Elderly patients and those with renal impairment are at an increased risk for Central Nervous System (CNS) adverse reactions. It is recommended that the dosage be reduced in these populations to mitigate potential risks.

Healthcare professionals should be aware that the absence of gastrointestinal (GI) symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation for GI malignancy is advised prior to the initiation of therapy to ensure patient safety.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions include headache, dizziness, constipation, and diarrhea.

In clinical trials, additional adverse reactions were observed across various systems. Notable reactions included fever, asthenia, and fatigue under the category of Body as a Whole. Cardiovascular effects such as palpitations were reported, along with gastrointestinal issues including elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth. Hematologic reactions included thrombocytopenia. Hypersensitivity reactions were noted, including orbital edema, rash, conjunctival injection, and bronchospasm. Musculoskeletal pain and arthralgia were also reported.

Nervous system and psychiatric adverse reactions included seizures, hallucinations, depression, anxiety, decreased libido, insomnia, and somnolence. Skin reactions such as pruritus, dry skin, and flushing were observed, as well as disturbances in special senses, including tinnitus and taste disorder. Other reactions included impotence.

Postmarketing experience has revealed further serious adverse reactions. Cardiovascular issues such as arrhythmia, AV block, and prolonged QT interval were reported. Gastrointestinal reactions included cholestatic jaundice and hepatitis. Hematologic concerns involved agranulocytosis, pancytopenia, and leukopenia. Hypersensitivity reactions were serious, with reports of anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal reactions included rhabdomyolysis and muscle cramps. Nervous system and psychiatric reactions such as confusion, agitation, and paresthesia were also noted. Respiratory adverse reactions included interstitial pneumonia, while skin reactions were severe, including toxic epidermal necrolysis and Stevens-Johnson syndrome.

It is important to note that elderly patients and those with renal impairment are at an increased risk for central nervous system adverse reactions, and dosage should be reduced accordingly. Additionally, the absence of gastrointestinal symptoms does not rule out the presence of gastric malignancy, necessitating evaluation prior to initiating therapy. A history of serious hypersensitivity reactions, such as anaphylaxis to famotidine or other H2 receptor antagonists, should be considered when prescribing this treatment.

Drug Interactions

Concomitant use of drugs that depend on gastric pH for absorption may significantly reduce systemic exposure of these agents, potentially leading to a loss of efficacy. Healthcare professionals are advised to consult the full prescribing information for a comprehensive list of interacting drugs.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when used with certain medications. This elevation can result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. It is recommended to avoid concomitant use of tizanidine with these interacting drugs whenever possible to mitigate these risks.

Packaging & NDC

The table below lists all NDC Code configurations of Famotidine, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of famotidine for oral suspension have been established in pediatric patients aged 1 year to less than 17 years for the treatment of peptic ulcer disease and gastroesophageal reflux disease (GERD), with or without esophagitis and ulcerations. This use is supported by evidence from adequate and well-controlled studies in adults, along with pharmacokinetic and pharmacodynamic data specific to this pediatric age group.

For infants from birth to less than 1 year of age, famotidine has been shown to be safe and effective for the treatment of GERD, with support from studies in adults and additional data in this younger population. However, the safety and effectiveness of famotidine for the treatment of peptic ulcer disease in patients less than 1 year of age have not been established.

Furthermore, the safety and effectiveness of famotidine for the treatment of pathological hypersecretory conditions and the reduction of the risk of duodenal ulcer recurrence have not been established in pediatric patients. It is also important to note that a safe and effective dosage has not been determined for pediatric patients with renal impairment.

Geriatric Use

Approximately 10% of the 1,442 patients treated with famotidine in clinical studies were aged 65 years and older. These studies did not reveal any overall differences in safety or effectiveness between elderly patients and their younger counterparts. However, caution is warranted when prescribing famotidine to geriatric patients, particularly those with renal impairment, as post-marketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in this population, regardless of renal function status.

Famotidine is primarily excreted by the kidneys, which may increase the risk of adverse reactions in elderly patients, especially those with compromised renal function. Therefore, it is recommended to use the lowest effective dose of famotidine for oral suspension in geriatric patients. Additionally, regular monitoring of renal function is advised to mitigate potential risks associated with its use in this demographic.

Pregnancy

Available data regarding the use of H2-receptor antagonists, including famotidine, in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of famotidine at doses up to approximately 243 and 122 times, respectively, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis.

The estimated background risk for major birth defects and miscarriage in the indicated population is unknown; however, all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is estimated to be 2% to 4% and 15% to 20%, respectively.

Reproductive studies conducted in rats and rabbits at oral doses of up to 2,000 and 500 mg/kg/day, respectively, as well as intravenous doses of up to 200 mg/kg/day in both species, have revealed no significant evidence of impaired fertility or harm to the fetus due to famotidine. While no direct fetotoxic effects have been observed, sporadic abortions were noted in some rabbits that exhibited marked decreased food intake at oral doses of 200 mg/kg/day (approximately 49 times the recommended human dose of 80 mg per day, based on body surface area) or higher.

There are, however, no adequate or well-controlled studies in pregnant women. Given that animal reproductive studies are not always predictive of human response, famotidine should be used during pregnancy only if clearly needed.

Lactation

There are limited data available on the presence of famotidine in human breast milk. Current evidence indicates that there were no effects observed on breastfed infants. However, there are no data regarding the effects of famotidine on milk production in lactating mothers.

In animal studies, famotidine has been detected in the milk of lactating rats. Notably, transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine, which were at least 600 times the usual human dose.

When considering the use of famotidine in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for famotidine and any potential adverse effects on the breastfed child from either the medication or the underlying maternal condition.

Renal Impairment

Patients with moderate and severe renal impairment may experience CNS adverse reactions and prolonged QT intervals. The clearance of famotidine is significantly reduced in these patients compared to those with normal renal function. For adults with mild renal impairment, defined as a creatinine clearance of greater than or equal to 60 mL/minute, no dosage adjustment is necessary. However, a dosage reduction is recommended for adults with moderate or severe renal impairment, where creatinine clearance is less than 60 mL/minute. Currently, data are insufficient to establish a safe and effective dosage for pediatric patients with renal impairment.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of famotidine overdosage, the adverse reactions observed are consistent with those associated with the administration of recommended dosages. Symptoms may include a range of gastrointestinal and central nervous system effects, mirroring the drug's known side effects.

Management of overdosage should be primarily symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract promptly. This may involve the use of activated charcoal or other appropriate measures, depending on the timing of the overdose and the clinical scenario. Continuous monitoring of the patient is crucial to assess for any developing symptoms and to provide necessary supportive therapy.

Due to famotidine's low binding affinity to plasma proteins, hemodialysis may facilitate its elimination from the body. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis in treating famotidine overdosage. Therefore, healthcare professionals should consider this option judiciously and in conjunction with other supportive measures.

Nonclinical Toxicology

Carcinogenic potential of famotidine was evaluated in a 106-week oral carcinogenicity study in rats and a 92-week oral carcinogenicity study in mice. In these studies, conducted at oral doses of up to 2,000 mg/kg/day (approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis, based on body surface area), no evidence of carcinogenic potential was observed.

Famotidine demonstrated a negative result in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli, both with and without rat liver enzyme activation, at concentrations up to 10,000 mcg/plate. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

In studies involving rats administered oral doses of up to 2,000 mg/kg/day (approximately 243 times the recommended human dose of 80 mg per day), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

During post-approval use of famotidine, various adverse reactions have been reported voluntarily from a population of uncertain size. Due to the nature of these reports, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular events include arrhythmia, AV block, and prolonged QT interval. Gastrointestinal reactions consist of cholestatic jaundice and hepatitis. Hematologic adverse events reported include agranulocytosis, pancytopenia, and leukopenia.

Hypersensitivity reactions have been noted, such as anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal issues include rhabdomyolysis and muscle cramps. Nervous system and psychiatric events reported are confusion, agitation, and paresthesia.

Respiratory adverse reactions include interstitial pneumonia, while skin reactions encompass toxic epidermal necrolysis and Stevens-Johnson syndrome.

Patient Counseling

Healthcare providers should advise elderly patients and those with moderate to severe renal impairment about the potential risk of central nervous system (CNS) adverse reactions associated with the medication. These reactions may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Patients should be instructed to report any of these symptoms immediately to their healthcare provider.

Additionally, it is important to inform patients with moderate and severe renal impairment about the risk of QT interval prolongation. They should be advised to report any new cardiac symptoms, such as palpitations, fainting, or feelings of dizziness or lightheadedness, to their healthcare provider without delay.

Patients and their caregivers should be instructed on the proper administration of famotidine, which should be taken once daily before bedtime or twice daily, in the morning and before bedtime, as recommended. It is also essential to inform them that famotidine can be taken with or without food, providing flexibility in its administration. Furthermore, patients and caregivers should be made aware that famotidine may be given concurrently with antacids, ensuring they understand the options available for managing their treatment effectively.

Storage and Handling

Famotidine for oral suspension is supplied as a dry powder that must be constituted prior to use. It should be stored at a controlled room temperature of 25°C (77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP guidelines. It is essential to protect the product from freezing to maintain its integrity.

Once constituted, the suspension must be discarded after 30 days if not used. For dispensing, it is required to utilize a USP tight, light-resistant container to ensure the product's stability and efficacy.

Additional Clinical Information

Postmarketing experience has revealed several adverse events associated with the use of the medication. Clinicians should be aware of potential cardiovascular issues, including arrhythmia, AV block, and prolonged QT interval. Gastrointestinal complications may manifest as cholestatic jaundice and hepatitis. Hematologic concerns include agranulocytosis, pancytopenia, and leukopenia.

Additionally, hypersensitivity reactions such as anaphylaxis, angioedema, facial edema, and urticaria have been reported. Musculoskeletal effects may involve rhabdomyolysis and muscle cramps. Neurologically, patients may experience confusion, agitation, and paresthesia. Respiratory complications, specifically interstitial pneumonia, and severe skin reactions like toxic epidermal necrolysis or Stevens-Johnson syndrome have also been documented.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Famotidine as submitted by Upsher-Smith Laboratories, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)